Diffusion tensor imaging (DTI) has a number of important applications including characterizing the effect of ischemic attacks and predicting the connectivity of the brain. Despite their clinical significance, diffusion images can suffer severe distortion due to the rapid switching of magnetic field gradients. This switching induces eddy currents in conductive materials (such as Faraday screens, RF coils, main magnet windings, and shim coils) within the field, which in turn generate induced magnetic fields that decay over time. The decay of these magnetic fields can be described as a series of exponentials with relatively long time constants (typically tens or hundreds of milliseconds)1,2. The induced time varying fields contain two components: a field gradient opposing the applied gradient, and a shift in the main magnetic field B0(t). This leads to unwanted phase dispersion of the net magnetization, which results in poor excitation of spins, imperfect rephasing of echoes, loss of signal and image distortion. Depending upon the direction of the eddy current relative to the imaging plane, the image can be sheared, scaled or translated in the phase encoding direction. In diffusion tensor imaging, the diffusion gradient amplitudes are often significantly larger than the imaging gradients and are often applied in several directions simultaneously. This leads to a complicated combination of shearing, scaling and translation.
In view of the above mentioned aspects of prior art it is the underlying purpose of the present invention to introduce an eddy current compensated and optimized imaging sequence which achieves improved imaging through optimization of signal to noise ratios of the detected signal while avoiding distortions in imaging due to magnetic fields associated with eddy currents.
The object of the invention is achieved with a method of eddy current compensated diffusion imaging using magnetic resonance in which a spin echo signal is obtained in a readout time window by excitation of a nuclear resonance signal using a first radio-frequency pulse. The first radio-frequency pulse is refocused using at least one second radio-frequency pulse and one third radio-frequency pulse. Gradient fields are applied, those fields having a direction and strength and being activated by means of gradient pulses, the gradient pulses located between each of the radio-frequency pulses and prior to the readout window. To generate an echo at the correct position within the readout time window, the totality of the gradient pulses has a gradient time integral between a time of said excitation and the center of kx (or center of k-space if there is a number of echoes for one excitation pulse) which is equal to zero. In this sequence, gradient pulses are applied with two-fold purpose:
1) Generation of spin echo image: These gradients are referred to as imaging gradients, applied for frequency encoding, at least one direction of phase encoding, and slice encoding. A number of echoes can be generated for one excitation RF pulse by using alternating frequency encoding gradients for each echo (echo-planar readout).
2) Generation of diffusion weighting: The diffusion gradient pulses have a polarity, which is alternated between successive gradient pulses. Although the totality of the gradient pulses having a gradient time integral between a time of said excitation and of the center of kx (or k-space if there is a number of echoes for one excitation pulse) is equal to zero, at least two of the gradient pulses have differing gradient time integrals in order to reduce problems due to stimulated echoes. In a subsequent method step in accordance with the invention, the gradient direction is changed and the previous steps are repeated to evenly distribute gradient direction vectors over a sphere.
The use of diffusion gradient pulses having alternate polarities in the manner described above and having a total gradient time integral of zero with at least two of the gradient pulses having differing gradient time integrals, provides a diffusion imaging method which is effective in avoiding distortions in the image due to eddy current production. By combining these features with a systematically changed gradient direction such that the gradient vectors are evenly distributed over a sphere, imaging distortions due to directional differences in the diffusion tensor are avoided.
In a preferred embodiment of the invention, time locations of the radio-frequency pulses, the time to the center of kx or k-space as well as the time of gradient pulses are adjusted to maximize diffusion parameter signal to noise ratio and to minimize eddy current field distortion at the center of kx or k-space. The signal to noise ratio tends to decrease with increasing time duration of the pulse sequence. However, later readout time windows are further removed from possible eddy current distortions caused by the switching of the gradient fields. Therefore, a compromise must be made between th e need for good signal to noise ratio while avoiding eddy current field distortions. By balancing these two conflicting requirements, an optimized pulse sequence can be obtained.
In a preferred improvement in this latter embodiment, the time locations are iteratively and systematically varied to obtain a relative maximum in the signal to noise ratio and a relative minimum in eddy current field distortions. This variation takes advantage of a two-dimensional correlation between the time dependences of the signal to noise ratio and eddy current distortion to optimize the pulse sequence. By iteratively and systematically varying the time locations of the radio frequency pulses and the gradient fields relative to the readout time window an optimized sequence can be obtained.
In a preferred embodiment, the time locations are analyzed as a function of echo times, defined by th e locations of the RF refocusing pulses. This embodiment has the advantage of taking into consideration the relationship between the echo time and the transverse relaxation time and their effects on the signal to noise ratio. The RF refocusing pulse time in spin echo sequences defines the echo time and therefore affects the overall time duration of the pulse sequence and the associated signal to noise ratio at readout.
In a further improvement, the time locations are analyzed as a function of gradient field durations. The gradient field durations affect the integral of the diffusion gradient field and therefore the overall strength of diffusion related signals while also directly influencing the overall time duration of the diffusion sequence and therefore the associated signal to noise ratios at readout.
In a further improvement, the time locations are analyzed as a function of an eddy current decay time. In this manner, an additional parameter influencing the time dependence of eddy currents is taken into consideration.
In a preferred embodiment of the invention, time locations are analyzed as a function of a number of measurements. The overall number of measurements taken to determine the diffusion tensor influences the signal to noise ratio at readout. Consideration of the number of measurements in defining the time locations for the gradient and RF excitation pulses permits an improved iterative optimization of these parameters.
In an associated improvement, the time locations are analyzed as a function of a gradient time integral. As previously mentioned, the overall time duration of the sequence as well as the strength of the gradient fields leading to observable diffusion effects directly depend on the gradient time interval. Taking this integral into consideration in determining the details of the pulse sequence therefore leads to improved signal to noise ratios and associated image quality.
In an improved method, the time locations are analyzed as a function of diffusivity. Clearly the overall image quality depends not only on the time duration of the pulse sequence and the other parameters mentioned above, but also on the diffusivity of the spin system being measured, since the sensitivity with which the diffusion tensor can be determined depends not only on the time relationships of the various pulses in the diffusion imaging pulse sequence but also on the measurement result itself. Therefore, this feature should be taken into consideration if an optimized pulse sequence is to be obtained.
In an improvement, (as mentioned above in relation to echo times) the time locations are analyzed as a function of transverse relaxation time. Since the signal to noise ratio depends on the transverse relaxation time, longer transverse relaxation times permit pulse sequences of longer duration. By taking into consideration these effects, the duration of the pulse sequence can be optimized for the spin system under study.
In a particularly preferred embodiment of the invention, the time locations of the various gradients and RF excitation pulse are analyzed and optimized using the following formula:       σ    D    =      σ    ⁢                            e                                    2              ⁢              TE                                      T              2                                      ⁡                  (                                                    N                H                            +                                                (                                      N                    -                                          N                      H                                                        )                                ·                                  e                                      2                    ⁢                                          b                      max                                        ⁢                    D                                                                                                      S                o                2                            ⁢                              b                max                2                            ⁢                                                N                  H                                ⁡                                  (                                      N                    -                                          N                      H                                                        )                                                              )                    
wherein "sgr"D is an error in a diffusion measurement, bmax a gradient time integral of a diffusion gradient, N a given number of measurements, NH a subset of measurements acquired at bmax, So an initial signal amplitude of moving spins in a diffusion weighted sequence, D a diffusivity, TE an echo time, T2 a transverse relaxation rate, and "sgr"2 a variance of a noise portion of a measured signal. By taking into account these parameters and their mutual functional relationship in the above mentioned formula, the image quality can be more precisely optimized.
In a preferred variation of this latter embodiment, the following formula is also used to determine the optimum time locations:
H(t)≅exe2x88x92xcexi(tD1+tD2+tD3+tD4+2t180+ts)xe2x88x92exe2x88x92xcexi(tD2+tD3+tD4+2t180+ts)xe2x88x92exe2x88x92xcexi(tD2+tD3+tD4+t180+ts)
+2exe2x88x92xcexi(tD3+tD4+t180+ts)xe2x88x92exe2x88x92xcexi(tD4+t180+ts)xe2x88x92exe2x88x92xcexi(tD4+ts)+exe2x88x92xcexi(ts)
wherein H(t) is a magnetic field due to eddy currents, xcexi a decay rate of eddy currents triggered by a rise and fall of gradients, i an index of a number of different decay rates generated for each gradient switching point, tDj a duration of a jth diffusion gradient, t180 a time of an RF refocusing pulse, and ts a delay before a center of an echo or a center of K-space.
By using the above formula, the time dependence of the distorting magnetic fields associated with eddy currents can be taken into consideration to time the gradients and the RF excitation signals as well as the readout time to avoid regions in which eddy currents are likely to upset or disturb the results of the diffusion imaging measurement. Both these parameters as well as their functional relationship are taken into consideration.
In a preferred embodiment of the invention, the gradient field strengths are adjusted and selected to maximize diffusion imaging sensitivity. This improvement of the invention takes into consideration the dependence of the result of the diffusion imaging measurement on the diffusivity of the medium being measured which, in turn, defines an optimum gradient field strength which takes into consideration the intrinsic diffusion performance of the spin system under study.
In a preferred embodiment of the invention, three diffusion gradients in three orthogonal spatial directions are simultaneously applied and the relative field strengths of these gradients are changed between successive iterations of the method, although the sum total vector gradient field strength is kept constant to maintain a maximum b-value. This particular measure has the advantage of using a minimum number of gradients to generate a gradient vector in an arbitrary spatial direction thereby allowing for a uniform filling of the directional vectors of the gradients on a sphere such that the results of the diffusion imaging measurement do not depend on directional anisotropies in the diffusion tensor.
In a preferred embodiment of this latter method variant, the three gradients are a frequency gradient, a phase gradient and a slice selection gradient. This embodiment has the advantage of utilizing normally existing gradients to effect an arbitrary gradient vector direction.
In a preferred embodiment of the method, a slice selection gradient is applied during a time duration of said radio frequency pulses. This measure has the advantage of more precisely defining an imaging slice by excitation of spins in that slice through adjustment of the frequency of the excitation pulse in dependence on the overall field strength within the slice.
In a preferred embodiment of the invention, a diffusion gradient pulse of a first polarity is activated between the first radio frequency pulse and the second radio pulse, with two gradient pulses of different polarity being subsequently activated between a second radio frequency pulse and a third radio frequency pulse, wherein the additional two gradient pulses begin with a polarity with its opposite to the first polarity of the first gradient pulse. Moreover, another gradient pulse is activated between a third radio frequency pulse and the readout window. This embodiment provides a simple pulse sequence, which satisfies the conditions for minimizing eddy current generation and the associated distorting magnetic fields at signal readout. The total gradient integral of the four diffusion gradient pulses must be equal to zero by the readout window, and preferably two individual time integrals must be different to avoid stimulated echoes.
In a preferred embodiment on the invention, activating a phase encoding gradient prior to the readout time window and activating a readout gradient during that readout time window spatially encode a spin echo signal. For each excitation pulse, either one readout gradient to obtain one echo, or a train of alternating polarity readout gradients (echo-planar readout) for a chain of echoes can be applied. In the case of an echo-planar readout, phase encoding for each echo occurs between each echo. This measure takes advantage of standard techniques in spin echo imaging to facilitate straightforward and economical data acquisition.
Further advantages of the invention can be derived from the associated description of the preferred embodiment in connection with the drawings. The features disclosed in the subsequent preferred embodiment, in the figures and in the attached claims can be important to the invention either singly or collectively in any arbitrary combination. The inventive embodiments disclosed are not considered to be exhaustive enumeration of all possible inventive configurations, rather have exemplary character for illustrating the invention. The invention is more closely described below in connection with the drawings.